7
Peracetic Acid1
Acute Exposure Guideline Levels

PREFACE

Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) has been established to identify, review and interpret relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 min (min) to 8 hs (h). Three levels—AEGL-1, AEGL-2 and AEGL-3—are developed for each of five exposure periods (10 and 30 min, 1 h, 4 h, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:


AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, non-sensory

1

This document was prepared by the AEGL Development Team composed of Kowetha Davidson (Oak Ridge National Laboratory) and Chemical Manager William Bress (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guideline reports (NRC 1993, 2001).



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7 Peracetic Acid1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guide- line Levels for Hazardous Substances (NAC/AEGL Committee) has been estab- lished to identify, review and interpret relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic chemicals. AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 min (min) to 8 hs (h). Three levels—AEGL-1, AEGL-2 and AEGL-3—are developed for each of five exposure periods (10 and 30 min, 1 h, 4 h, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows: AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, non-sensory 1 This document was prepared by the AEGL Development Team composed of Kowetha Davidson (Oak Ridge National Laboratory) and Chemical Manager William Bress (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifi- cally valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guideline reports (NRC 1993, 2001). 327

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328 Acute Exposure Guideline Levels effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure. AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape. AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience life-threatening health effects or death. Airborne concentrations below the AEGL-1 represent exposure levels that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, non-sensory effects. With increasing airborne concentrations above each AEGL, there is a progres- sive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations, such as in- fants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experi- ence the effects described at concentrations below the corresponding AEGL. SUMMARY Peracetic acid is produced by the catalytic action of sulfuric acid on acetic acid and hydrogen peroxide. Technical or commercial peracetic acid products contain different concentrations of peracetic acid, acetic acid, and hydrogen per- oxide, but the concentration of peracetic acid does not exceed 40%. Peracetic acid is unstable; it decomposes to its original constituents under conditions that vary with concentration, temperature, and pH. Peracetic acid is used as a disin- fectant against bacteria, fungi, and viruses in the food and medical industry, as a bleaching agent, as a polymerization catalyst or co-catalyst, in the epoxidation of fatty acid esters, as an epoxy resin precursor, and in the synthesis of other chemicals. Peracetic acid is corrosive/irritating to the eyes, mucous membranes of the respiratory tract, and skin. It causes lacrimation, extreme discomfort, and irrita- tion to the upper respiratory tract in humans after exposure to concentrations as low as 15.6 mg peracetic acid/m3 (5 ppm) for only 3 min. Eye irritation, clinical signs, and pathologic lesions indicative of respiratory tract irritation have been observed in laboratory animals exposed by inhalation to various concentrations of peracetic acid aerosols. Exposure to lethal concentrations of peracetic acid causes hemorrhage, edema, and consolidation of the lungs, whereas nonlethal concentrations cause transient weight loss or reduced weight gain in addition to slight to moderate signs of respiratory tract irritation. Human data were available

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329 Peracetic Acid for deriving AEGL-1 and -2 values and animal data were available for deriving AEGL-3 values. The AEGL-1 value is 0.52 mg/m3 (0.17 ppm) for all exposure durations from 10 min to 8 h. This value was derived from an exposure concentration of 1.56 mg/m3 (0.5 ppm), which, according to Fraser and Thorbinson (1986), is expected to cause no discomfort and according to McDonagh (1997) is not im- mediately irritating but would be unpleasant for an extended period of time. Therefore, 1.56 mg/m3 is considered to be the threshold for irritation to mucous membranes and eyes. An intraspecies uncertainty factor of 3 was applied to 1.56 peracetic acid mg/m3, because peracetic acid is a corrosive/irritant substance and the effects, which are confined to the upper respiratory tract, are expected to be similar for individuals within the population. The rationale for proposing the same value for all time points, is as follows: (1) effects of peracetic acid expo- sure correlate with concentration more than time, and (2) and peracetic acid is freely soluble in water; therefore, it should be effectively scrubbed in the nasal passages, particularly at the very low AEGL-1 concentration. The AEGL-2 value is 1.56 mg/m3 (0.5 ppm) for all exposure durations from 10 min to 8 h based on an exposure concentration of 4.7 mg/m3, which, according to Fraser and Thorbinson (1986), is expected to be associated with slight to tolerable discomfort to nasal membranes and eyes for exposure dura- tions up to 20 min. There was no increase in irritation with exposure duration. An intraspecies uncertainty factor of 3 was applied because peracetic acid is a corrosive/irritating substance and the effects, which are confined to the upper respiratory tract, are expected to be similar among individuals in the population. The rationale for proposing the same value for all exposure durations is dis- cussed above for AEGL-1 values. The AEGL-3 values are derived from the study of Janssen (1989). This study showed that rats exposed to Proxitane 1507 (15% peracetic acid, ~28% acetic acid, 14% hydrogen peroxide, ~1% “stabilizer,” and ~43% water) aero- sols at concentrations of 130, 300, or 320 mg/m3 for 30 min had mortality re- sponses of 0/5, 0/5, and 3/5 rats, respectively. Exposures to aerosol concentra- tions of 150, 390, or 1450 mg/m3 for 60 min resulted in the death of 0/5, 2/5, and 5/5 rats, respectively. Clinical signs indicative of respiratory tract irritation were observed at all concentrations and increased in severity with increased ex- posure concentration for each exposure duration. Clinical signs suggestive of nervous system effects were also observed, but could have been due to extreme respiratory tract discomfort. The AEGL values were derived from the highest concentration at which no mortality was observed: 300 mg/m3 for a 30-min ex- posure and 150 mg/m3 for a 60-min exposure. The total uncertainty factor is 10. Interspecies and intraspecies uncertainty factors of 3 were applied because mu- cous membranes of the respiratory tract are not expected to show significant variation in response to corrosive/irritating substances concentrations that cause physical damage and that approach the threshold for lethality regardless of spe- cies or the individuals in the population. The data, however, suggest that humans may be slightly more sensitive than animals to peracetic acid. The rationale for

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330 Acute Exposure Guideline Levels the intraspecies uncertainty factor of 3 was the same as described for AEGL-1. The intraspecies uncertainty factor of 3 and the interspecies uncertainty factor of 3 were applied to 300 and 150 mg/m3 for the 30- and 60-min exposures, respec- tively. The equation, Cn × t = k, where n = 1.6 (estimated from 1- and 4-h LC50 data for rat), was used to scale the 60-min exposure to 4- and 8-h values and the 30-min exposure to 10 min. The AEGL values are summarized in Table 7-1. 1. INTRODUCTION Peracetic acid is produced by the catalytic action of sulfuric acid on acetic acid and hydrogen peroxide (Lewis 1993). These constituents are found in the most concentrated commercial grades of peracetic acid at the following ap- proximate concentrations (weight %): 40% peracetic acid, 40%, acetic acid, 5% hydrogen peroxide, 1% sulfuric acid, and 13% water, along with 500 ppm of a “stabilizer” (Bock et al. 1975). The stabilizer was not identified. Peracetic acid decomposes as it is diluted with water, particularly when diluted to 10 or 20% peracetic acid. Sulfuric acid catalyzes the decomposition of peracetic acid and is present in sufficient amounts in 10 to 20% peracetic acid products to catalyze the decomposition of peracetic acid to the individual constituents: acetic acid and hydrogen peroxide. At more dilute concentrations of peracetic acid, decom- position occurs more slowly, because sulfuric acid is no longer present in suffi- cient quantities to catalyze its decomposition. However, very dilute solutions (0.2%) will decompose more rapidly at elevated temperatures (4 weeks at 4ºC vs 1 week at 40 ºC). In addition, increasing the pH to 7.0 results in greater than 50% decomposition of peracetic acid after 1 day compared with almost no de- composition after 7 days at pH 2.7 (the natural pH of 0.2% peracetic acid) (Mucke 1977). Peracetic acid is known as a powerful oxidizing agent. It is un- stable upon contact with organic materials and it explodes at 110ºC (Lewis 1993). Because of its effectiveness against bacteria, fungi, and viruses, peracetic acid is used as a disinfectant in the food and medical industries (Bock et al. 1975; Fishbein 1979; Lewis 1993). It is also used as a beaching agent in the pa- per and textile industries, as a polymerization catalyst or co-catalyst, in the ep- oxidation of fatty acid esters, as an epoxy resin precursor, and in the synthesis of other chemicals (Bock et al. 1975; Fishbein 1979). The database for peracetic acid is limited; however, limited quantitative human and animal data are available for deriving AEGL values. The animal data for inhalation studies were performed primarily on aerosols of trade name prod- ucts or diluted grades of peracetic acid referred to as Proxitane 1507 (15% per- acetic acid, ~28% acetic acid, and 14% hydrogen peroxide) or Proxitane AHC (~5% peracetic acid, 19% (minimum) hydrogen peroxide, and 10% acetic acid). Measurements of atmospheric concentrations in the inhalation chambers showed

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331 Peracetic Acid TABLE 7-1 Summary of AEGL Values for Peracetic Acid Classification 10 min 30 min 1h 4h 8h End Point /Reference AEGL-1 0.52 0.52 0.52 0.52 0.52 Threshold for irritation (Nondisabling) mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 (Fraser and Thorbinson (0.17 (0.17 (0.17 (0.17 (0.17 1986; McDonagh 1997) ppm) ppm) ppm) ppm) ppm) AEGL-2 1.6 1.6 1.6 1.6 1.6 Mild irritation (Fraser mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 (Disabling) and Thorbinson 1986) (0.5 (0.5 (0.5 (0.5 (0.5 ppm) ppm ppm) ppm) ppm) AEGL-3a 60 30 15 6.3 4.1 Highest concentration mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 (Lethal) causing no deaths (Janssen 1989a) a AEGL-3 values are based on exposure to aerosol; therefore, concentrations are not con- verted to ppm. that the relative concentrations of peracetic acid, acetic acid, and hydrogen per- oxide varied in aerosols generated from the same product, thus demonstrating the instability of peracetic acid in the product or the aerosol. Although a contrib- uting effect of acetic acid and hydrogen peroxide cannot be ruled out in the tox- icity studies described in this report, it appears, however, that acetic acid and hydrogen peroxide are considerably less toxic than peracetic acid. Sulfuric acid concentrations were not reported for the products (Proxitane 1507 and Proxitane AHC) used in these studies, but would be expected to account for only a very small fraction since the highest concentration of sulfuric acid in most products was only 1%. The physical and chemical data for peracetic acid are presented in Table 7-2. 2. HUMAN TOXICITY DATA 2.1. Acute Lethality No data on human lethality due to exposure to peracetic acid were found in the literature searched. 2.2. Nonlethal Toxicity Bock et al. (1975) reported that peracetic acid was intensely irritating to the human nasal passages. There was no additional information documenting the source of this information. McDonagh (1997) and an associate conducted meas- urements of airborne peracetic acid concentrations in two caprolactone distilla- tion plants. Peracetic acid, which is used in caprolactone monomer production, was distilled in the distillation houses of the plant. The monitoring took place

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332 Acute Exposure Guideline Levels over a 3-h period. Peracetic acid vapor was measured at total peroxygen content; hydrogen peroxide was not expected to comprise a large proportion of the meas- ured substance in the vapor. In one area, peracetic acid concentrations ranged from 0.5 to 0.6 ppm (1.56-1.87 mg/m3); these concentrations were not consid- ered to be immediately irritating, but would have been considered Aunpleasant for an extended period@ of time. Peracetic acid concentrations of 0.13 to 0.17 ppm (0.40-0.53 mg/m3) in another area were considered tolerable and not un- pleasant. McDonagh and his associate spent most of their time in an area where the average peracetic acid concentration measured for a 10-min sampling time was 0.17 ppm (0.53 mg/m3). They noted no lacrimation at any time during their 3-h exposure. McDonagh (1997) recommended 0.15 ppm (0.47 mg/m3) as an acceptable 8-h occupational exposure limit for peracetic acid. This concentration would be perceptible, but not irritating or unpleasant. TABLE 7-2 Physical and Chemical Data for Peracetic Acid Parameter Data Reference Chemical Name Peracetic acid O’Neil et al. 2001 Synonyms Peroxyacetic acid, acetic peroxide, O’Neil et al. 2001; ethaneperoxoic acid, acetyl RTECS 2003 hydroperoxide, Proxitane 4002, Proxitane 1507, Proxitane AHC CAS Registry No. 79-21-0 RTECS 2003 Chemical Formula CH3COOOH O’Neil et al. 2001 Molecular Weight 76.05 O’Neil et al. 2001 Physical State Colorless liquid Lewis 1993 Boiling/Freezing/ 105 ºC/-30 ºC/40.5 ºC Lewis 1993 Flash Point Density 1.15 at 20 ºC Lewis 1993 Freely soluble in H2O, alcohol, Solubility O’Neil et al. 2001 ether, H2SO4 Vapor Pressure 14.5 mm Hg at 25ºC HSDB 1997 Explosion point 110 ºC Lewis 1993 -6 3 Henry’s Law Constant 2.08 × 10 atmm /mol at 25 ºC HSDB 1997 3 Conversion factors 1 ppm= 3.04 mg/m at 20 ºC IUCLID 2000 and 101kPa 1mg/ m3= 0.33 ppm

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333 Peracetic Acid Fraser and Thorbinson (1986) conducted fogging studies in a chicken house using Tenneco Organics’ “Peratol” diluted to 1:20 (5% peracetic acid = 1904 mg/L in the liquid formulation) to determine atmospheric levels of per- oxygen and establish safe working practices. Measurements of aerosol concen- trations were taken at various distances from the fogging unit to establish the spread and distribution of peracetic acid concentrations. The analytical proce- dure measured total peroxygen concentration, which was calculated as hydrogen peroxide (H2O2). The details of the analytical method were not presented in the report. The fogging unit was placed about 1 m off the ground, and measure- ments were taken at various locations (the shed apex, the floor, and sides of the shed). The first half of Table 7-3 presents the concentrations, time of measure- ments starting at 3:30 (p.m. assumed), and physiological responses to peracetic acid. The authors did not report the number of subjects exposed to the aerosol. Lacrimation was noted at 5 ppm (15.6 mg/m3), extreme discomfort was noted at concentrations ≥2.5 ppm (7.79 mg/m3), and 2.0 ppm (6.23 mg/m3) was consid- ered unbearable in one instance and tolerable for 2 min in another. After 23 min, the fogging unit was turned off and refilled; during this time, the concentration of peracetic acid dropped to <0.5, 0.5- 1.0, and 1.0-1.5 ppm (1.56, 1.56-3.12, and 3.12-4.7 mg/m3) at 0.3, 2, and 4 meters, respectively, above ground; a slight discomfort of nasal and eye membranes was noted during this phase. For the next 1 h and 15 min, the concentrations ranged from 2.0 to 3.0 ppm (6.23 to 9.35 mg/m3); these concentrations were associated with unbearable or extreme dis- comfort. At 5:20 p.m., the fogger was turned off and the concentrations of peracetic acid began to decrease. The second half of Table 7-3 describes the concentra- tions and observed physiological responses after shutoff. After the fogger was turned off, the concentrations on peracetic acid decreased from 2.0 ppm (6.23 mg/m3) to #0.5 ppm within 45 min. During this time the physiological responses decreased from extreme discomfort of mucous membranes to mild discomfort at 0.5-1.0 ppm (1.56-3.12 mg/m3) to no discomfort at ≤ 0.5 ppm (1.56 mg/m3). No irritation to the chest occurred at any time during this test. 2.3. Summary No data on human lethality caused by exposure to peracetic acid were found in the literature, and the data on nonlethal effects are limited. Peracetic acid is extremely irritating to mucous membranes of the eyes and nasal passages at low concentrations. Exposure to aerosols generated from diluted Peratol was associated with lacrimation at 5 ppm (15.6 mg/m3), extreme discomfort and irri- tation to mucous membranes at $2.0 ppm (6.23 mg/m3); slight or mild discom- fort at 0.5-1.5 ppm (1.56-4.67 mg/m3), and no discomfort at <0.5 ppm (1.56 mg/m3) (Fraser and Thorbinson 1986). Exposure to peracetic acid vapor at con- centrations of 0.13-0.17 ppm ( 0.40-0.53 mg/m3) for up to 3 h were detectable, tolerable, and not unpleasant (McDonagh 1997). Irritation to the chest did not

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334 Acute Exposure Guideline Levels occur at concentrations ≥5 ppm (15.6 mg/m3), and no data were available for exposure of humans to concentrations >5 ppm (15.6 mg/m3). In the study by McDonagh (1997), humans were exposed to peracetic acid vapor, and in the study by Fraser and Thorbinson (1986) humans were exposed to the aerosols. There was agreement between exposure to aerosol and vapors at 0.5 ppm (1.56 mg/m3), the highest vapor concentrations reported; both studies reported either no discomfort or only mild or slight discomfort at this concentration. There were no comparable levels between the two studies at the higher exposure concentra- tions. TABLE 7-3 Physiologic Response to Low Level Exposure to Peracetic Acid Aerosols Generated by a Fogger ppm (as total H2O2)a Time Observed Effects 3.30 5 (15.6) Lacrimation, extreme discomfort, irritation of nasal membranes 3.37 5 (15.6) Lacrimation, extreme discomfort, irritation of nasal membranes 3.53 1 to 1.5 (3.12-4.67) Slight discomfort of nasal and eye membranes, decreasing with concentration 0.5 to 1.0 (1.56-3.12) <0.5 (1.56) 4.05 2.0 (6.23) Irritation considered unbearable 5.00 2.5 (7.79) Extreme discomfort of nasal membranes 5.10 2.5 (7.79) Extreme discomfort 3.0 (9.35) Extreme discomfort 5.15 3.0 (9.35) Extreme discomfort 5.20 2.0 (6.23) Irritation tolerable for 2 min Concentrations and response after the fogger was turned off (minutes) 5 - 10 2.0 (6.23) Extreme discomfort of mucous membranes 15-20 1to 1.5 (3.12-4.67) Discomfort of mucous membranes 25 1.0 (3.12) Discomfort tolerable 30 0.5 to 1.0 (1.56-3.12) Discomfort mild 35- 45 ≤ 0.5 (1.56) No discomfort a Measurements taken at different locations relative to fogging unit; numbers in parentheses are concentrations in mg/m3. Source: Fraser and Thorbinson 1986. Reprinted with permission; copyright 1986, Solvay SA.

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335 Peracetic Acid 3. ANIMAL TOXICITY DATA 3.1. Acute Lethality 3.1.1. Rats Janssen (1989a) conducted a study in which groups of five male CPB-WU Wistar derived rats were exposed to Proxitane 1507 (15% peracetic acid, ~28% acetic acid, 14% hydrogen peroxide, ~1% stabilizer, and ~43% water) aerosol by nose-only inhalation in a 40 L dynamic flow chamber. The chamber was con- structed of aluminum, and the inside walls were coated with silver and a thin layer of polytetrafluoroethylene. The test atmospheres were generated with a stainless-steel nebulizer, and test concentrations were analyzed as total peroxy- gen concentration corrected for the amount of hydrogen peroxide. Chamber concentrations (converted from mg/L to mg/m3) of the constituents in the test material and exposure durations are listed in Table 7-4. The study author did not comment on the greater than zero concentration of constituents in the control atmosphere, but it may be related to the detection limit of the analytical proce- dure or natural occurrence of hydrogen peroxide in the atmosphere (ATSDR 1998). Respiratory rates were determined during exposure, clinical signs of tox- icity were recorded for 14 days after exposure, and body weight was measured on post-exposure days 2, 7, and 14. Postmortem studies included gross examina- tion, measurement of lung weight, and histopathological examination of the lungs. The results are summarized in Table 7-4. Deaths occurred only in groups exposed to peracetic concentrations ≥320 mg/m3 regardless of exposure duration (320 mg/m3 for 15 or 30 min, 390 mg/m3 for 60 min, and 1450 mg/m3 for 60 min). The LC50 for the 60-min exposure to peracetic acid was 476 mg/m3. Clinical signs of toxicity included effects primar- ily indicative of extreme respiratory irritation (reduced respiratory rate, respira- tory difficulties, blood around the nose and mouth, sneezing, and rubbing the nose) and those that may be indicative of nervous system effects (passivity, de- creased alertness and startle response, piloerection, salivation, decreased coordi- nation and muscle tone), but were probably related to extreme discomfort of the animals. The only effect on the eyes was drooping eye lids. The severity of the clinical signs (slight, moderate, severe) as well as the number of signs observed in each group and time of disappearance of clinical signs increased with concen- tration of test material and exposure duration. Clinical signs disappeared 1.5 h to 5 days after exposure. Respiratory rates measured during exposure showed maximum depressions to 22 to 41% of preexposure rates in all exposure groups. Body weight measurements showed transient decreases on day 2 after exposure to 320 mg/m3 for 15 or 30 min and 150 mg/m3 or 1450 mg/m3 for 60 min.

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TABLE 7-4 Effects of Nose-Only Inhalation Exposure to Proxitane 15077 in Male Rats 336 Concentration (mg/m3)a Effects Group Exposure Peracetic Acetic Clinical Signs and Gross Number Time (min) Acid Acid Mortality Body Weighta Pathology H2O2 10 (control) 60 <70 <70 <50 0/5 + URT (0/5); LRT (1/5) 8 15 300 767 <50 0/5 +, bw (no effect) URT (0/5); LRT (2/5) 3 15 320 2000 <70 1/5 +, ++, wt. loss URT (1/5); LRT (1/5) 6 30 130 210 10 0/5 +, bw (no effect) URT (0/5); LRT (0/5) 9 30 300 767 <50 0/5 +, ++, bw (no effect) URT (0/5); LRT (1/5) 4 30 320 2000 <70 3/5 +, ++, +++, bw (no data) URT (2/5); LRT (5/5) 7 60 150 290 9 0/5 URT (0/5); +, ++, 9 bw LRT (1/5) 5 60 390 2800 4 2/5 +, ++, +++, bw (no data) URT (2/5); LRT (4/5) 2 60 1450 6600 450 5/5 +, ++, +++, bw (no data) URT (3/5); LRT (2/5) a +, ++, +++ refer to slight, moderate, and severe clinical signs, respectively. Abbreviations: bw = body weight; 9 = decrease; URT = upper respiratory tract; LRT = lower respiratory tract. Source: Janssen 1989a.

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337 Peracetic Acid Macroscopic examinations showed effects indicative of respiratory irrita- tion (blood around the nose, red nasal and tracheal mucosa, bloody fluid in the trachea, dark red lungs, and red or dark spots on the lungs) particularly in ani- mals that died during the study. The animals surviving to study termination showed only red or dark spots on the lungs. In addition, the stomach and small intestines were distended with gas and the liver was swollen in animals exposed to ≥320 mg/m3. Absolute and relative lung weights were elevated in rats ex- posed to 320 or 390 mg/m3. Only one animal each exposed to 300, 390, or 1450 mg/m3 showed microscopic effects in the lungs. Although it appeared that the observed effects were caused by exposure to peracetic acid, most effects also showed increased severity with the increased concentrations of measured acetic acid and hydrogen peroxide. Based on lethality data, it is unlikely that acetic caused the effects observed in the rats; however, a contributing effect cannot be ruled out for either constituent. See Section 4.4.4. for a brief discussion of the toxicity of acetic acid and hydrogen peroxide (Janssen 1989a). Janssen and Van Doorn (1994) conducted a 4-h acute inhalation study in rats with Proxitane AHC. The chemical composition of the test material was as follows: 4.7 to 5.4% (~5%) peracetic acid, 19% (minimum) hydrogen peroxide, 10% acetic acid, water, and 1% surfactant. Groups of five male and five female Wistar derived rats were exposed to aerosols of the test material by nose-only inhalation in an aluminum chamber with the inside walls coated with silver and a thin layer of polytetrafluoroethylene. The test concentrations of peracetic acid in the chamber were analyzed as total peroxygen concentration corrected for the amount of hydrogen peroxide. The concentrations of peracetic acid and other constituents are presented in Table 7-5. Each group was exposed to the test at- mospheres for 4 h and surviving animals were observed for 14 days. An unex- posed control group was included. The mortality response is summarized in Ta- ble 7-5 In Group B exposed to peracetic acid at 267 mg/m3, four of five male rats died by day 3 and all females had died by day 4 (four died before day 2). In Group D exposed to 185 mg/m3, two males died on day 1 and two females had died by day 3. The LC50 for the combined sexes was 204 mg/m3. Numerous clinical signs including apathy, respiratory difficulties, reduced respiratory rate, noisy breathing, cyanosis, lacrimation, salivation, ptosis, twitching, hypother- mia, abnormal gait and posture, crusts on nose, and blood under cage were ob- served in rats of all groups except lacrimation, cyanosis, and salivation were not observed at 87 mg/m3. Fewer clinical signs were observed in the lowest expo- sure group compared with the highest exposure groups. The clinical signs disap- peared after day 1 for males or day 3 for female rats exposed to 87 mg/m3 and after day 3 or 4 for the remaining groups. The clinical signs were considered to be related to the corrosive/irritant properties of the test material. The body weights of rats exposed to the test atmospheres were much less than those of the controls on day 2 after exposure due to pronounced weight losses of 36 to 52 g for males and 19 to 34 g for females (p<0.01 all groups compared with controls). Body weights of all exposed groups showed signs of recovery between day 2

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357 Peracetic Acid TABLE 7-12 AEGL-3 Values for Peracetic Acid 10 min 30 min 1h 4h 8h 60 mg/m3 30 mg/m3 15 mg/m3 6.3 mg/m3 4.1 mg/m3 TABLE 7-13 Summary of AEGL Values for Peracetic Acid Classification 10 min 30 min 1h 4h 8h End Point /Reference AEGL-1 0.52 0.52 0.52 0.52 0.52 Threshold for (Nondisabling) mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 irritation (Fraser and (0.17 (0.17 (0.17 (0.17 (0.17 Thorbinson 1986; ppm) ppm) ppm) ppm) ppm) McDonagh 1997) AEGL-2 1.6 1.6 1.6 1.6 1.6 Mild irritation mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 (Disabling) (Fraser and (0.5 (0.5 (0.5 (0.5 (0.5 Thorbinson 1986) ppm) ppm ppm) ppm) ppm) AEGL-3 60 30 15 6.3 4.1 Highest concentration mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 (Lethal) causing no deaths (Janssen 1989a) SLV-EEI-3 (death/permanent incapacity) = 50 ppm (156 mg mg/m3): the threshold above which mortality and/or irreversible effects could be observed for an exposure of up to 60 min. SLV-EEI-2 (disability) = 3 ppm (9 mg mg/m3): the threshold level above which intense lacrimation, extreme nose discomfort and transient incapacitation (inability of self-protection but without residual consequences) could be ob- served for an exposure of up to 60 min. SLV-EEI-1(discomfort) = 0.15 ppm (0.45 mg mg/m3): the threshold level above which discomfort could be observed for an exposure of up to 8 h per day. 8.3. Data Quality and Research Needs Human data on exposure to peracetic acid were limited. This substance is corrosive to mucous membranes causing extreme discomfort depending on the concentration. Therefore, additional humans studies would not be feasible ex- cept for very low concentrations (below irritation levels in normal subjects) us- ing healthy exercising subjects. The animal studies found in the literature were well conducted considering the circumstances. Peracetic acid occurs in mixtures with acetic acid, hydrogen peroxide, a stabilizer, and sometimes sulfuric acid. Commercial preparations vary in the concentrations of the three components. Because of the instability of peracetic acid, the aerosol or vapor may have dif- ferent compositions of peracetic acid, acetic acid, and hydrogen peroxide. Varia- tions in the composition of the test material could lead to inconsistencies in the

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358 Acute Exposure Guideline Levels observed effects. Therefore, acute inhalation studies using the same commercial product to study lethal and nonlethal effects after exposure for 30 min, and 1, 4, and 8 h would aid in the evaluation of the toxicity of peracetic acid. 9. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists, Inc.). 1991. Hy- drogen peroxide. Pp. 782-783 in Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th Ed. American Conference of Governmental Industrial Hygienists, Inc., Cincinnati, OH. ACGIH (American Conference of Governmental Industrial Hygienists, Inc.). 2004. Ace- tic acid. In Documentation of the Threshold Limit Values and Biological Exposure Indices, 2004 Supplement to the 7th Ed. American Conference of Governmental Industrial Hygienists, Inc., Cincinnati, OH. Agnet, Y., J.L. Dorange, and P. Dupuy. 1976. Mutagenicity of peracetic acid on Salmo- nella typhimurium. Mutat. Res. 38(2):119 [Abstract 33]. ATSDR (Agency for Toxic Substances and Disease Registry). 1998. Toxicological Pro- file for Sulfur Trioxide and Sulfuric Acid. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Regis- try, Atlanta, GA. December 1998 [online]. Available: http://www.atsdr.cdc.gov/ toxprofiles/tp117.pdf [accessed Nov. 12, 2008]. Benes, V., B. Tichacek, and J. Veger. 1966. Toxizizat der Peressigsaure. Pp. 114-124 in Peressigsäure und die Moglichkeit ihrer Verwertung in der Desinfektion, B.Tichacek, ed. Prag: Staatsverlag für Gesundheitswesen der CSSR (as cited in Heinze et al. 1979). Bock, F.G., H.K. Meyers, and H.W. Fox. 1975. Cocarcinogenic activity of peroxy com- pounds. J. Natl. Cancer Inst. 55(6):1359-1361. Bulnes, C., M.G. Garcia, and L. Tablada. 1982. Toxic effects of peracetic acid. II. Mor- phopathological study following direct contact with guinea pig skin [in Spanish]. Rev. Salud. Anim. 4 (4):59-65. Fishbein, L. 1979. Peroxides. Pp. 158-161 in Potential Industrial Carcinogens and Mutagens. Studies in Environmental Science 4. New York: Elsevier. Fraser, J.A.L., and A. Thorbinson. 1986. Fogging Trials with Tenneco Organics Limited (30th June, 1986) at Collards Farm. Solvay Interox, Warrington, UK. Friebig, U, and G. Reuter. 1975. Anatomisch-pathologische und histopathologische Untersuchungen der Lunge, Leber und Niere sowie Untersuchung der Aktivitat der Serum-Glutamat-Oxalazetat-Transminase im Blutserum von Schweinen und Kabern nach der Desinfektion mit PES-Aerosol. Vet.-med. Diplomarbeit Berlin (as cited in Heinze et al. 1979). Galvin, J.B., and C. Farr. 1993. Organic peroxides. Pp. 527-597 in Patty’s Industrial Hy- giene and Toxicology, Vol. II, Part A Toxicology, 4th Ed., G.D. Clayton, and F.E. Clayton, eds. New York: John Wiley & Sons. Heinze, W., E. Werner, S. von Krüger, and G. Wilsdorf. 1979. On the tolerance of per- acetic acid aerosols with particular attention to impaired defense mechanisms [in German]. Monatsh. Veterinarmed. 34:212-217. HSDB (Hazardous Substances Data Bank). 1997. Peracetic Acid. TOXNET, Specialized Information Services, U.S. National Library of Medicine, Bethesda, MD [online].

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359 Peracetic Acid Available: http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~T7RRWD:1 [ac- cessed Nov. 13, 2008]. IARC (International Agency for Research on Cancer). 1985. Hydrogen peroxide. Pp. 285-314 in Allyl Compounds, Aldehydes, Epoxides and Peroxides. IARC Mono- graphs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans Vol. 36. Lyon, France: IARC. IUCLID (International Uniform Chemical Information Database). 2000. Peracetic Acid (CAS No. 79-21-0). IUCLID Dataset. 2000 CD-room Ed. European Commission, European Chemical Bureau [online]. Available: http://ecb.jrc.it/IUCLID-Data Sheets/79210.pdf [accessed Nov. 25, 2008]. Janssen, P.J.M. 1989a. Acute Inhalation Toxicity Studies of Proxitane 1507 in Male Rats (I). Report No. S. 8906, Int. Doc. No. 56645/25/89. Duphar B.V., Weesp, The Netherlands, and Solvay, Brussels, Belgium. Janssen, P.J.M. 1989b. Acute Inhalation Toxicity Studies of Proxitane 1507 in Male Rats (II). Report No. S. 8908, Int. Doc. No. 56645/34/89. Duphar B.V., Weesp, The Netherlands, and Solvay, Brussels, Belgium. Janssen, P.J.M. 1989c. Acute Inhalation Study to Investigate the Respiratory Irritating Properties of Proxitane 1507 in Male Rats. Report No. S. 8912, Int. Doc. No. 56645/40/89. Duphar B.V., Weesp, The Netherlands, and Solvay, Brussels, Bel- gium. Janssen, P.J.M. 1990. Preliminary Acute Inhalation Study to Investigate the Respiratory Irritating Properties of Proxitane 1507 in Male Rats. Report No. S.9003, Int. Doc. No. 56645/33/90. Duphar B.V., Weesp, The Netherlands, and Solvay, Brussels, Belgium. Janssen, P.J.M., and W.M. van Doorn. 1994. Acute Inhalation Toxicity Study with Proxi- tane AHC in Male and Female Rats. Report No. S. 9408, Int. Doc. No. 56345/48/94. Duphar B.V., Weesp, The Netherlands, and Solvay, Brussels, Bel- gium. Katz, G.V., and D. Guest. 1994. Aliphatic carboxylic acids. Pp. 3523-3671 in Patty’s Industrial Hygiene and Toxicology, Vol. 2E, 4th ed., G.D. Clayton, and F.E. Clay- ton, eds. New York: John Wiley & Sons. Koch, S., A. Kramer, J. Stein, V. Adrian, and W. Weuffen. 1989. Mutagenicity testing in sperm-head test/mouse and mutagenic potency of 2 disinfectants on the basis of peracetic acid and phenolics respectively [in German]. Zentralbl. Hyg. Umwelt- med. 188(5):391-403. Krüger, S., and D. Kruschinski. 1982. On the acute inhalation toxicity of peracetic acid aerosols in mice [in German]. Wiss. Z. Humboldt-Univ. Berlin Mat.-Nat. 31:543- 548. Lai, D.Y., Y.T. Woo, M.F. Argus, and J.C. Arcos. 1996. Carcinogenic potential of or- ganic peroxides: Prediction based on structure-activity relationships (SAR) and mechanism-based short-term tests. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 14(1):63-80. Lewis, R.J., ed. 1993. Pp. 883-884 in Hawley’s Condensed Chemical Dictionary, 12th Ed. New York: Van Nostrand Reinhold. McDonagh, J. 1997. Atmospheric Monitoring of Peracetic Acid on the Existing Caprolactone Plant Distillation Houses A and B, Assessment of Results. Document No. EE970192.M01. Memorandum to R.A. Haffenden et al., from J. McDonagh, Solvay Interox, Warrington. April 30, 1997.

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360 Acute Exposure Guideline Levels Merka, V., and R. Urban. 1978. Study of inhalation toxicity of performic, peracetic and perpropionic acid in mice. J. Hyg. Epidemiol. Microbiol. Immunol. 20(1):54-60. Mücke, H. 1970. The properties of peracetic acid: Excerpts relating to the bactericidal, sporicidal, viricidal and fungicidal effect of peracetic acid [in German]. Zeitschrift der Universität Rostock 3:267-270. Mücke, H. 1977. Studies on effects on the decomposition of dilute peracetic acid [in German]. Pharmazie. 32(10):613-619. NIOSH (National Institute of Occupational Safety and Health). 1996a. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLH): NIOSH Chemical Listing and Documentation of Revised IDLH Values (as of 3/1/95)- Hydrogen Peroxide. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute of Occupational Safety and Health [online]. Available: http://www.cdc.gov/niosh/idlh/772841.html [ac- cessed Nov. 6, 2008]. NIOSH (National Institute of Occupational Safety and Health). 1996b. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLH): NIOSH Chemical Listing and Documentation of Revised IDLH Values (as of 3/1/95)- Acetic Acid. U.S. Department of Health and Human Services, Centers for Dis- ease Control and Prevention, National Institute of Occupational Safety and Health [online]. Available: http://www.cdc.gov/niosh/idlh/64197.html [accessed Nov. 6, 2008]. NRC (National Resource Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 1993. Guidelines for Developing Community Emer- gency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press. NRC (National Research Council). 1984. Sulfuric acid. Pp. 107-112 in Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 1. Wash- ington, DC: National Academy Press. Oberst, F.W., C.C. Comstock, and E.B. Hackley. 1954. Inhalation toxicity of ninety per- cent hydrogen peroxide vapor; acute, subacute, and chronic exposure to laboratory animals. AMA Arch. Ind. Health 10(4):319-327. O’Neil, M.J., A. Smith, P.E. Heckelman, J.R. Obenchain, Jr., J. Gallipeau, and M.A. D’Arecca. 2001. Peracetic acid. P. 1283 in The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 13th Ed. Whitehouse Station, NJ: Merck. Paldy, A., G. Berensci, A. Kramer, W. Weuffen, and E. Spiegelberger. 1984. Mutagens potency of Wofasteril, Wofasept, formaldehyde, chlorhexidine, and Bronopol in the bone marrow of mice. Pp. 349-352 in Aspects of Prevention and Control of Hospital Infections, A. Kramer, H. Wigert, and B. Kemter, eds. Microbial Envi- ronment and Antimicrobial Measures, Vol. 8 [in German]. Leipzig: Barth. RTECS (Registry of Toxic Effects of Chemical Substances). 2003. Peroxyacetic Acid. RTECS No. SD8750000. National Institute for Occupational Safety and Health [online]. Available: http://www.msdshazcom.com/RTECS/SD8583B0.HTM [ac- cessed Nov. 14, 2008]. SOLVAY. 1998. SOLVAY Emergency Exposure Indices for Accidental Exposure to Peracetic Acid. SOLVAY, Brussels, Belgium. Sterner, J.H. 1943. Determining margins of safety: criteria for defining a “harmful” expo- sure. Ind. Med. 12:514-518 (as cited in ACGIH 2004).

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361 Peracetic Acid Uhlemann, F. 1971. P. 13 in Forschungsabschlußbericht: Aerosldesinfektion in tierpro- duktionsanlagen. Karl-Marx-Stadt (as cited in Kruger and Kruschinski 1982). Vigliani, E.C., and N. Zurlo. 1955. Erfahrungen der Clinica del Lavoro mit einigen maximalen Arbeitsplatzkonzentrationen (MAK) von Industriegiften. Arch Gewer- bepath. Gewerbehyg. 13(5):528-535. [Abstract in Arch. Ind. Health 13:403 (1956)](as cited in ACGIH 2004). Whitman, F.T. 1991. Acute Inhalation toxicity study of peracetic acid 0.15 use dilution (MRK-91-004) in the rat. Final Report. Performed by Exxon Biomedical Sciences, Inc, East Millstone NJ, for FMC Corporation, Princeton, NJ. Yin, M., Y. Chen, and J. Wang. 1989. Studies on the genotoxicity of disinfectants with SOS chromotest. Environ. Mol. Mutagen. 14 (Suppl. 15):225-226.

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362 Acute Exposure Guideline Levels APPENDIX A Derivation of AEGL Values for Peracetic Acid Derivation of AEGL-1 Key Study: McDonagh 1997; Fraser and Thorbinson 1986 Toxicity End Point: Threshold for irritation Time Scaling: Not applicable. Uncertainty Factors: NA for interspecies sensitivity (AEGL-1 derived from human data). 3 for intraspecies variability; peracetic acid is corrosive and response to upper respiratory tract and eyes is expected to be similar among individuals in the population. Modifying Factor: 1 1.56 mg/m3/3 = 0.52 mg/m3 Calculations: The same value applied for 10-min to 8-h exposure durations. Derivation of AEGL-2 Key Study: Fraser and Thorbinson 1986 Toxicity End Point: Slight upper respiratory tract irritation. Uncertainty Factor: NA for interspecies sensitivity (AEGL-2 derived from human data). 3 for intraspecies variability; peracetic acid is corrosive and effects in the upper respiratory tract are expected to be similar among individuals in the population. Modifying Factor: 1 4.67 mg/m3 /3 = 1.6 mg/m3 Calculations: The same value applied to 10-min to 8-h durations.

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363 Peracetic Acid Derivation of AEGL-3 Key Study: Janssen 1989a Toxicity End Point: Highest nonlethal concentration of 96 ppm for a 30-min exposure and 48 ppm for a 60-min exposure in the rat. Cn × t = k; n = 1.6 based on analysis of rat lethality data. Time Scaling: Uncertainty Factors: 3, for interspecies sensitivity: mucous membranes of the respiratory tract of humans and animals are not expected to show vast differences in response to corrosive/irritant substances at concentrations that cause severe physical damage or at the threshold for lethality. 3, for intraspecies variability: mucous membranes of individuals are not expected to show a great difference in response to a corrosive/irritant substance such as peracetic acid. Modifying Factor: 1 Calculations: C = (k/t)1/1.6 = (6927 mg/m3 min/10 min)1/1.6 10-min AEGL-3 C = 59.6 = 60 mg/m3 300 mg/m3/10 (uncertainty factor) = 30 mg/m3 30-min AEGL-3 Cn × t = k; C = 30 mg/m3, t = 30 min, n = 1.6 k = 6927 mg/m3•min C = (k/t)1/1.6 = (6927 mg/m3 min/30 min)1/1.6 C = 30 mg/m3 150 mg/m3/10 (uncertainty factor) = 15.0 mg/m3 1-h AEGL-3 Cn × t = k; C = 15 mg/m3, t = 60 min, n = 1.6 k = 4569.8008 mg/m3•min C = (k/t)1/1.6 = (4570 mg/m3 min/60 min)1/1.6 C = 15 mg/m3 C = (k/t)1/1.6 = (4570 mg/m3 min/240 min)1/1.6 4-h AEGL-3 C = 6.3 mg/m3 C = (k/t)1/1.6 = (4570 mg/m3 min/480 min)1/1.6 8-h AEGL-3 C = 4.1 mg/m3

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364 Acute Exposure Guideline Levels APPENDIX B Derivation Summary: AEGLs for Peracetic Acid AEGL-1 VALUES 10 min 30 min 1h 4h 8h 3 3 3 3 0.52 mg/m3 0.52 mg/m 0.52 mg/m 0.52 mg/m 0.52 mg/m ( 0.17 ppm) ( 0.17 ppm) ( 0.17 ppm) ( 0.17 ppm) (0.17 ppm) Key References: (I) McDonagh, J. 1997. Atmospheric Monitoring of Peracetic Acid on the Existing Caprolactone Plant Distillation Houses A and B, Assessment of Results. Document No. EE970192.M01. Memorandum to R.A. Haffenden et al., from J. McDonagh, Solvay Interox, Warrington. April 30, 1997. (II) Fraser, J.A.L., and A. Thorbinson. 1986. Fogging Trials with Tenneco Organics Limited (30th June, 1986) at Collards Farm. Solvay Interox, Warrington, UK. Test Species/Strain/Number: Humans/two subjects (I); number unknown (II) Exposure Route/Concentration/Durations: Inhalation, 0.40-0.53 mg/m3 (0.13-0.17 ppm) for up to 3 h (I); 1.56-1.87 mg/m3 (0.5-0.6 ppm) for unknown time (I), <1.56-4.67 mg/m3 for 12 min; ≤1.56 to ≥6.23 mg/m3 for 45 min (II). Effects: 1.56-3.12 mg/m3: mild discomfort 1.56-1.87 mg/m3: no immediate irritation; may be unpleasant for extended period. ≤1.56 mg/m3: no discomfort. 0.40-0.53 mg/m3: detectable, but tolerable and not unpleasant. End Point/Concentration/Rationale: Threshold for irritation of 1.56 mg/m3; the effects range from detectable but tolerable and not unpleasant to no discomfort. Uncertainty Factors/Rationale: Total uncertainty factor: 3 Interspecies: Not applicable. Intraspecies: 3, individuals in the population are expected to respond similarly and by a factor no greater than 3 when exposed to corrosive/irritant agents that affect the upper respiratory tract. Modifying Factor: 1 Animal to Human Dosimetric Adjustment: Not applicable. Time Scaling: Not applicable. Data Adequacy: Human data were limited but were generally supported by animal data. The human data showed that irritation or discomfort at concentrations≤1.56 mg/m3 is expected to be absent or minimal. Neither study reported the number of subjects exposed to peracetic acid.

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365 Peracetic Acid AEGL-2 VALUES 10 min 30 min 1h 4h 8h 1.6 mg/m3 1.6 mg/m3 1.6 mg/m3 1.6 mg/m3 1.6 mg/m3 (0.5 ppm) (0.5 ppm) (0.5 ppm) (0.5 ppm) (0.5 ppm) Key Reference: Fraser, J.A.L., and A. Thorbinson. 1986. Fogging Trials with Tenneco Organics Limited (30th June, 1986) at Collards Farm. Solvay Interox, Warrington, UK. Test Species/Strain/Number: Humans, number exposed is unknown. Exposure Route/Concentration/Durations: Inhalation, range of 15.6 mg/m3 for 7 min; <1.56-4.67 mg/m3 for 12 min; 6.23-9.35 mg/m3 for 1 h and 15 min; ≤1.56-6.23 mg/m3 for 45 min. Effects: All effects were associated with the upper respiratory tract or eyes. 6.23-15.6 mg/m3: lacrimation, extreme upper respiratory discomfort or irritation 6.23 mg/m3: unbearable irritation or extreme discomfort, but tolerable for 2 min 3.13-4.67 mg/m3: slight or tolerable discomfort (upper respiratory tract and eyes) 1.36-3.12 mg/m3: mild discomfort; ≤1.56 mg/m3: no discomfort. End Point/Concentration/Rationale: Slight upper respiratory tract irritation at 4.7 mg/m3 Uncertainty Factors/Rationale: Total uncertainty factor: 3 Interspecies: Not applicable. Intraspecies: 3, individuals in the population are expected to respond similarly and by a factor no greater than 3 when exposed to corrosive/irritant agents that affect the upper respiratory tract. Modifying Factor: 1 Animal to Human Dosimetric Adjustment: Not applicable. Time Scaling: Not applicable. Data Adequacy: The number of subjects exposed to peracetic acid was not reported by the investigators. The AEGL-2 value was based on a concentration that caused discomfort or slight discomfort, which is below the definition for AEGL-2; the next higher concentrations caused unbearable irritation after 2 min. Therefore, the lower concentration was more appropriate for deriving AEGL-2 values. The rationale for selecting the same value for all time points is as follows: (1) effects of peracetic acid exposure correlate with concentration more than time, and (2) peracetic acid is freely soluble in water and should be effectively scrubbed in the nasal passages, particularly at the very low AEGL-2 concentration.

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366 Acute Exposure Guideline Levels AEGL-3 VALUES 10 min 30 min 1h 4h 8h 60 mg/m3 30 mg/m3 15 mg/m3 4.1 mg/m3 6.3 mg/m3 Key Reference: Janssen, P.J.M. 1989a. Acute Inhalation Toxicity Studies of Proxitane 1507 in Male Rats (I). Report No. S. 8906, Int. Doc. No. 56645/25/89. Duphar B.V., Weesp, The Netherlands, and Solvay, Brussels, Belgium. Test Species/Strain/Number: Rat/ CPB-WU Wistar/5 males per group. Exposure Route/Concentration/Durations: Inhalation: 130, 300, or 320 mg/m3 for 30 min and 150, 390, or 1450 mg/m3 for 60 min. Effects: Clinical signs: signs of extreme respiratory irritation and discomfort, drooping eyelids, transient weight loss, reduced respiratory rate. Gross pathologic effects: blood around nose, red nasal and tracheal mucosa, bloody fluid in trachea, dark red lungs, red or dark spots on lungs, elevated lung weight Mortality: 0/5 rats at 300 mg/m3 and 3/5 at 320 mg/m3 for 30 min; 0/5 at 150 mg/m3, 2/5 at 390 mg/m3, and 5/5 at 1450 mg/m3 for 60 min. End Point/Concentration/Rationale: Highest non-lethal concentrations for rats exposed for 30 or 60 min; the concentrations were 300 mg/m3 for 30 min and 150 mg/m3 for 60 min. Uncertainty Factors/Rationale: Total uncertainty factor: 10 Interspecies: 3, mucous membranes of the respiratory tract of humans and animals are not expected to show vast differences in response to corrosive/irritant substances at concentrations that cause severe physical damage or at the threshold for lethality. Intraspecies: 3, mucous membranes of individuals are not expected to show a great difference in response to a corrosive/irritant substance such as peracetic acid. Modifying Factor: 1 Animal to Human Dosimetric Adjustment: 1 Time Scaling: Cn × t = k, where n = 1.6 based on analysis of rat LC50 data for 1 and 4 h exposures. Data Adequacy: The animal studies were well conducted; however, the different compositions of peracetic acid probably contributed to the inconsistencies of the results. The animal studies were conducted with aerosols instead of the vapor.

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APPENDIX C Category Plot for Peracetic Acid Chemical Toxicity - TSD All Data Peracetic acid 10000.0 Human - No Effect Human - Discomfort 1000.0 Human - Disabling Animal - No Effect 100.0 Animal - Discomfort ppm 10.0 Animal - Disabling AEGL-3 Animal - Some Lethality AEGL-2 1.0 Animal - Lethal AEGL-1 AEGL 0.1 0 60 120 180 240 300 360 420 480 Minutes FIGURE C-1 Category plot for peracetic acid. 367